Impact of pre‐therapy glioblastoma multiforme microenvironment on clinical response to autologous CMV‐specific T‐cell therapy
DG Walker, R Shakya, B Morrison… - Clinical & …, 2019 - Wiley Online Library
Clinical & translational immunology, 2019•Wiley Online Library
Objectives Clinical response to antibody‐based immunotherapies targeting checkpoint
inhibitors is critically dependent on the tumor immune microenvironment (TIME). However,
the precise impact of the TIME on adoptive cellular immunotherapy remains unexplored.
Here we have conducted a long‐term follow‐up analysis of patients with recurrent
glioblastoma multiforme (GBM) who were treated with autologous CMV‐specific T‐cell
therapy to delineate the potential impact of the TIME on their clinical response. Methods …
inhibitors is critically dependent on the tumor immune microenvironment (TIME). However,
the precise impact of the TIME on adoptive cellular immunotherapy remains unexplored.
Here we have conducted a long‐term follow‐up analysis of patients with recurrent
glioblastoma multiforme (GBM) who were treated with autologous CMV‐specific T‐cell
therapy to delineate the potential impact of the TIME on their clinical response. Methods …
Objectives
Clinical response to antibody‐based immunotherapies targeting checkpoint inhibitors is critically dependent on the tumor immune microenvironment (TIME). However, the precise impact of the TIME on adoptive cellular immunotherapy remains unexplored. Here we have conducted a long‐term follow‐up analysis of patients with recurrent glioblastoma multiforme (GBM) who were treated with autologous CMV‐specific T‐cell therapy to delineate the potential impact of the TIME on their clinical response.
Methods
Multiplexed immunohistochemical analysis of CD3, PD‐L1 and Sox‐2 in GBM tissue biopsies obtained before autologous T‐cell therapy was carried out and correlated with long‐term survival of GBM patients adoptively treated with T‐cell therapy.
Results
Tumor microenvironment analyses revealed that the pre‐treatment cellular composition of the tumor tissue may influence the subsequent response to adoptive T‐cell therapy. GBM patients who showed prolonged overall survival following T‐cell therapy had a significantly lower number of tumor‐infiltrating CD3+ T cells in recurrent tumors than that in patients with short‐term survival. Furthermore, long‐term surviving patients showed low or undetectable PD‐L1 expression in tumor cells in recurrent GBM biopsies.
Conclusion
We hypothesise that lack of PD‐L1‐mediated immunosuppression in the TIME may allow efficient immune control following adoptive T‐cell therapy. Future studies combining anti‐PD‐L1 or genetically modified T cells with PD‐1 receptor knockdown could be considered to improve clinical responses in patients who have high PD‐L1 expression in their tumors.
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